We report the synthesis, characterization, antibacterial and antifungal activities, phytotoxicity, and genotoxicity of two new complexes of silver(I) with sulfachloropyridazine (SCP), one of which is heteroleptic with SCP and SCN(-) ligands (Ag-SCP-SCN), the other of which is homoleptic (Ag-SCP); furthermore, the crystal structure of the homoleptic complex is disclosed. The heterocyclic N atom nearest to the Cl atom and the N(sulfonamide) atom could be coordination sites for the silver ion in the Ag-SCP-SCN complex. The Ag-SCP complex is a polymeric compound with metal-metal bonds, and the heterocyclic and sulfonamide N atoms are points of coordination for Ag(I) . Both complexes showed activity against all the tested bacteria, and in the cases of Escherichia coli and Pseudomonas aeruginosa, the action was better than that of SCP. In all cases, both silver-SCP complexes showed better antifungal activity than SCP, which was inactive against the tested fungi. Notably, the activity against P. aeruginosa, a nosocomial multidrug-resistant pathogen, was better than that of the reference antibiotic cefotaxim. Both silver-sulfa complexes displayed moderate activity against the tested yeast, especially for C. neoformans, which is an important fact considering the incidence of cryptococcosis, mainly in immune-deficient patients. No chromosomal aberrations were observed with the Allium cepa test, which is auspicious for further study of these complexes as potential drugs.
Objective: To describe the occurrence of a subdural hematoma in a woman undergoing chemotherapy with cyclophosphamide, methotrexate, and fluorouracil combined with warfarin therapy.Case Summary: A 60-year-old white woman with atrial fibrillation underwent radical mastectomy for primary breast cancer with histologically positive axillary lymph nodes. Following surgery, the patient received adjuvant chemotherapy with a CMF 1-8 regimen consisting of cyclophosphamide 100 mg/m 2 orally on days 1-14, methotrexate 40 mg/m 2 intravenously, and fluorouracil 600 mg/m 2 by intravenous bolus on days 1 and 8 every 4 weeks. Warfarin 5 mg/day was administered concomitantly due to atrial fibrillation. Following the second course of concomitant therapy, the patient developed a headache, hemiparesis, and an international normalized ratio (INR) of 7.6, which was highly suggestive of a drug interaction between fluorouracil and warfarin. A computed tomography scan of the brain revealed a left parieto-occipital subdural hematoma.Discussion: This case emphasizes the importance of the potentially fatal drug interaction involving warfarin and fluorouracil.
Conclusions: Several adverse interactions between warfarin and fluorouracil have been reported.Considering the severity of this interaction, close monitoring of the INR is recommended in patients receiving these agents concomitantly.
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